Menthol Binding and Inhibition of α7-Nicotinic Acetylcholine Receptors
Menthol Binding and Inhibition of α7-Nicotinic Acetylcholine Receptors
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DOI：
10.1371/journal.pone.0067674
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发表时间：
2013-07-23
期刊：
影响因子：
3.7
通讯作者：
Oz, Murat
中科院分区：
文献类型：
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作者：
Ashoor, Abrar;Nordman, Jacob C.;Oz, Murat
薄荷脑是一种常见的药物和商业产品中的化合物，也是一种流行的香烟添加剂。薄荷醇的分子靶点仍然不明确。在这项研究中，我们显示了薄荷醇对烟碱乙酰胆碱（nACh）受体功能的α（7）亚基的影响。使用双电极电压钳技术，薄荷醇被发现可逆地抑制α（7）-nACh受体异源表达在非洲爪蟾卵母细胞。薄荷醇的抑制作用不依赖于膜电位，也不涉及内源性Ca 2+依赖性Cl-通道，因为薄荷醇的抑制作用通过细胞内注射Ca 2+螯合剂BAPTA和用含有Ba 2+的无钙洗浴液灌注保持不变。此外，增加乙酰胆碱浓度并没有逆转薄荷醇的抑制和[I-125] α-银环蛇毒素的特异性结合没有减弱薄荷醇。对神经细胞中内源性表达的α（7）-nACh受体的研究表明，薄荷醇减弱细胞体和神经突中α（7）介导的Ca 2+瞬变。总之，我们的研究结果表明，薄荷醇抑制α（7）-nACh受体以非竞争性的方式。
Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the alpha(7) subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit alpha(7)-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca2+-dependent Cl- channels, since menthol inhibition remained unchanged by intracellular injection of the Ca2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing Ba2+. Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [I-125] alpha-bungarotoxin was not attenuated by menthol. Studies of alpha(7)-nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates alpha(7) mediated Ca2+ transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits alpha(7)-nACh receptors in a noncompetitive manner.